'Fat But Fit' Only Transient State on Risk Pathway

Not a stable or reliable indicator of future cardiovascular disease, study shows

Kate Kneisel, Contributing Writer, MedPage Today; Henry A Solomon, MD, FACP, FACC, Clinical Associate Professor, Weill Cornell Medical College, Reviewer; and Dorothy Caputo, MA, BSN, RN, Nurse Planner have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staff of Projects In Knowledge®, Inc. and the staff of MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

by Kate Kneisel, Contributing Writer, MedPage Today
April 23, 2018

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Action Points

Metabolically healthy obesity (MHO) is neither a stable nor reliable indicator of future risk for cardiovascular disease (CVD), since almost one-half of those with MHO and no cardiovascular risk at baseline developed metabolic syndrome (MetS) during follow-up, resulting in increased odds of cardiovascular disease (CVD).

Realize that these and other data indicating that MHO alone is not a stable or reliable characterization of lower clinical risk suggest that constant vigilance is necessary to avoid transitioning from MHO to metabolic syndrome and the associated increased likelihood of incident CVD.

Metabolically healthy obesity (MHO) is neither a stable nor reliable indicator of future risk for cardiovascular disease (CVD), despite having a risk similar to that of being normal weight at baseline, according to a longitudinal analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants.

Almost one-half of those with MHO and no CV risk at baseline developed metabolic syndrome (MetS) during follow-up, resulting in increased odds of CVD (OR 1.60, 95% CI 1.14 to 2.25) compared with those with stable MHO or having healthy normal weight, reported Morgana Mongraw-Chaffin, PhD, of Wake Forest School of Medicine in Winston-Salem, N.C., and colleagues.

The duration of MetS was associated with CVD in a significant and linear dose-response fashion -- one visit with MetS OR 1.62, two visits OR 1.92, three or more visits OR 2.33, P value for trend <0.001 -- and MetS mediated approximately 62% (44-100%) of the relationship between obesity at any point during follow-up and CVD, the group wrote in the Journal of the American College of Cardiology.

"... Metabolically healthy obesity signals an opportunity for weight reduction, and prevention and management of existing metabolic syndrome components should be prioritized."

Similar findings have been reported in studies of European and British populations. Despite some conflicting research, and unexplained heterogeneity in overweight populations in the literature, "accumulating evidence is leaning toward the consensus that MHO is not a low-risk state compared with metabolically healthy normal weight," the team wrote. "The likelihood of underestimating risk based on MHO at a single time point has clear implications for clinical practice and resource management."

Of the more than 6,800 participants in the population-based longitudinal cohort MESA study, 5,005 were included in the primary analysis of transition from MHO to MUO; at baseline, 2,254 individuals were obese -- defined as having a body-mass index of 30 or more -- 1,051 were MHO, and 1,203 were MUO.

Participants were considered to have MUO if they met three or more of the Harmonized International Diabetes Federation criteria: elevated levels of triglycerides, high-density lipoprotein cholesterol, blood pressure, fasting glucose, or waist circumference (>102 cm in men and >88 cm in women).

Baseline demographic and socioeconomic factors differed significantly between the metabolic status groups, as did statin use, but not total or low-density lipoprotein cholesterol or current smoking status.

Clinical evaluation of obesity and metabolic syndrome components was repeated every 2 years, for a total of five study visits. Over a median follow-up of 12.2 years, 791 cardiovascular disease events and 975 deaths were recorded.

The researchers said that although the full mechanisms for the pathway from obesity to MetS to CVD remain unknown, this study and others increasingly explain variations in the relationship through differences in exposure to obesity: "Consistent with our results, a growing consensus indicates that when obesity and MetS are considered together for CVD and mortality, obesity is not an independent risk factor."

Writing in an accompanying editorial, Prakash Deedwania, MD, of the University of California at San Francisco School of Medicine, and Carl J. Lavie, Jr., MD, of the Ochsner Health System in New Orleans and the University of Queensland-Ochsner Medicine Program, said: "Besides prevention of obesity and progressive weight gain, the study also emphasizes the importance of preventing the development of metabolic syndrome, and treating it adequately if it develops. The best treatment of metabolic syndrome may be vigorous nonpharmacologic therapy, including prevention of further weight gain with increasing physical activity/exercise training along with dietary restrictions ... and pharmacologic treatment of [cardiovascular risk factors]."

Indeed, the editorialists noted that while it is often understated, "cardiorespiratory fitness may be more important than weight for predicting long-term prognosis ... and should be assessed, given evidence that obese people, especially those with MHO, with relatively preserved cardiorespiratory fitness have an excellent prognosis."

Study limitations, Mongraw-Chaffin et al wrote, included that the research may have been inadequately powered to fully assess interactions and interpret results for certain subgroups; there may have been potential differential loss of some participants to follow-up; and MESA had limited measurement of physical activity and cardiorespiratory fitness.

The study was supported by the National Heart, Lung, and Blood Institute, and the National Center for Research Resources.

One co-author reported previously employment at Merck Research Laboratories, but stated that the company "played no role in any aspect of the research." Mongraw-Chaffin and the other co-authors reported having no relationships relevant to the study.

Deedwania and Lavie also reported that they have no relationships relevant to the contents of their editorial.

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